title: P21-activated kinase 1 promotes colorectal cancer survival by up-regulation of hypoxia-inducible factor-1α.
abstract: P21 activated kinase 1 (PAK1) enhances colorectal cancer (CRC) progression by stimulating Wnt/β-catenin and Ras oncogene, which promote CRC survival via stimulation of hypoxia-inducible factor 1α (HIF-1α). The aim of this study was to assess the mechanism involved in the stimulation by PAK1 of CRC survival. PAK1 promoted CRC cell survival by up-regulation of HIF-1α. PAK1 was over-expressed and hyper-activated in tumors of ApcΔ(14/+) mice, which was correlated with over-expression of HIF-1α and β-catenin. Inhibition of PAK1 decreased tumor growth and the expression of HIF-1α and β-catenin in tumors of ApcΔ(14/+) mice, and suppressed xenograft tumor survival in SCID mice. These findings indicate that PAK1 stimulates CRC survival by up-regulation of HIF-1α.
authors.affiliation: Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Victoria 3084, Australia.
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Liu
authors.forename: Nhi
authors.initials: N
authors.lastname: Huynh
authors.forename: Oneel
authors.initials: O
authors.lastname: Patel
authors.forename: Arthur
authors.initials: A
authors.lastname: Shulkes
authors.forename: Graham
authors.initials: G
authors.lastname: Baldwin
authors.forename: Hong
authors.initials: H
authors.lastname: He
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000628:therapy; D004789:Enzyme Activation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D034741:RNA, Small Interfering / Q000235:genetics; D047368:Tumor Burden; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D054462:p21-Activated Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C495270:CTNNB1 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; C515903:PAK1 protein, human; D054462:p21-Activated Kinases
keywords: CRC; HIF-1α; PAK1; β-Catenin